How Doctors Grade Glioblastoma Brain Tumors

Glioblastoma arises from normal cells called glial cells, which are the scaffolding that holds the brain together. To be more precise, the disease arises from a certain kind of glial cell called an astrocytoma. Astrocytomas help to nourish neurons and form scar tissue when the brain is damaged. (1)

The disease was first identified in the second half of the 19th century. It is known more formally as glioblastoma multiforme. The first surgery performed on a patient with this type of tumor was done in Vienna in 1904.

The incidence of glioblastoma is higher among Caucasians, especially if they live in industrial areas.

Doctors do not fully understand the cause of these tumors. They arise spontaneously but sometimes develop in members of the same family, and they can also occur in patients with certain genetic diseases; both these observations suggest a possible genetic component.

Glioblastomas are also more common in postmenopausal women, raising the question of whether hormones might be involved, and in taller, heavier people. These tumors rarely occur in children and infants. (2)

The prognosis for patients with glioblastoma is usually not good, although it is gradually improving. Mark Gilbert, MD, the chief of the National Institute of Health’s Neuro-Oncology Branch, says, “We have seen incremental improvements in survival. The median length of survival was only 8 to 10 months in the mid-1990s, but it has almost doubled to 15 to 18 months now.” (3)

One of the ways to determine the outlook for a particular patient with other cancers is to stage the tumor when a patient is diagnosed, from stage 1 (least advanced) to stage 4 (most advanced). Each cancer stage is based on the size of the primary tumor, whether and how far it has spread through the body, and a variety of other factors.

But brain tumors are different. They usually do not spread outside of the brain, and they are graded, not staged. Those tumors with the highest grades tend to grow faster and spread more quickly.

The first thing that is usually done to grade a brain tumor is to extract some cancer cells with a biopsy and examine them under a microscope. Doctors determine a grade based primarily on this microscopic examination.

Tumor grade is based in part on how abnormal the tumor cells look, and on special stains performed on the biopsy, which are indicators of how fast the tumor is growing. (4)

Some cells might look only slightly different from normal cells. They are referred to as “well-differentiated,” and they tend to grow more slowly than other tumors. Tumor cells with a very abnormal appearance, lacking structures found in normal cells, are classified as “undifferentiated” or “poorly differentiated.”

The World Health Organization’s tumor grading system is widely used:

• Grade 1: These tumors typically grow slowly and do not grow into (invade or infiltrate) nearby tissues. They can often be cured with surgery.
• Grade 2: These tumors also tend to grow slowly but they can grow into nearby brain tissue. They are more likely than grade 1 tumors to come back after surgery. They are also more likely to become faster-growing tumors over time.
• Grade 3: These tumors look more abnormal under the microscope. They can grow into nearby brain tissue and are more likely to need other treatments in addition to surgery.
• Grade 4: These are the fastest-growing tumors. They generally require the most aggressive treatment. (5)

Because brain tumors do not have a formal staging system, oncologists consider other factors when trying to predict a patient’s outlook. Here are some of those factors, according to the American Cancer Society:

• Age
• Functional level; whether the tumor is affecting normal brain functions and everyday activity
• The grade of the tumor; how quickly the tumor is likely to grow, based on how the cells look under a microscope
• If the tumor cells have certain gene mutations or other changes; for example, tumors with a mutation in the IDH1 or IDH2 gene, known as “IDH-mutant” tumors, tend to grow more slowly and have a better outlook than tumors without these mutations
• The location and size of the tumor
• How much of the tumor can be removed by surgery (if it can be done)
• Whether or not the tumor has spread through the cerebrospinal fluid to other parts of the brain or spinal cord
• Whether or not tumor cells have spread beyond the central nervous system (6)

A patient’s symptoms can also help determine the outcome. Seizures and having symptoms for a long time are linked with a better prognosis.

Yet another indication of a glioblastoma patient’s outlook is what happens following surgery. Oncologists refer to the portion of the tumor remaining in the brain as the residual tumor. And this, too, is broken down into categories:

• Gross Total The entire tumor was removed, but microscopic cells may remain.
• Subtotal Large portions of the tumor were removed.
• Partial Only part of the tumor was removed.
• Biopsy Only Only a small portion, used for a biopsy, was removed. (7)